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Biomedical subjects

S Sved

Publications and source records attributed to S Sved.

At least 19 recordsLinked to original sources

In vitro germicidal activity of teat dips against Nocardia asteroides and other udder pathogens.

Nine commercial teat dip formulations containing 1.94% linear dodecylbenzene sulfonic acid, or 1% available iodine from nonylphenoxypoly (ethyleneoxy) ethanol-iodine complex, or .5% chlorhexidine acetate were tested for contamination with aerobic and anaerobic bacteria and their in vitro germicidal activity against Staphylococcus aureus, Streptococcus agalactiae, Escherichia coli, and Nocardia asteroides. All products were free of bacteria when neutralized samples were tested on blood agar or liquid thioglycollate media. To test for in vitro efficacy, each teat dip preparation was mixed with a suspension of one of the pathogenic test organisms containing 10(8) bacteria/ml (final concentration) for .5 to 15 min. Viable bacteria were evaluated by direct plating of neutralized aliquots and by filtration techniques. All products were effective against E. coli, Staph. aureus, and Strep. agalactiae. With N. asteroides, the direct plating method gave equivocal results. The filtration experiments indicated that all teat dips containing dodecylbenzene sulfonic acid and nonylphenoxypoly (ethyleneoxy) ethanol-iodine complex were effective against all four pathogens. Three of the teat dips containing chlorhexidine acetate were ineffective against N. asteroides. The fourth teat dip, containing chlorhexidine acetate and an emollient, was partially effective.

Animals

Use of liquid chromatography in the synthesis of isoluminol-labeled medroxyprogesterone acetate and zeranol.

A high-performance liquid chromatographic (HPLC) method for monitoring the syntheses of two isoluminol-labelled drugs, medroxyprogesterone acetate (MPA) and zeranol, has been developed. MPA and the ketone derivative of zeranol, zearalanone, were conjugated to N-(4-aminobutyl)-N-ethylisoluminol through the carboxymethyloxime derivative of the drug by using the N-succinimide ester as an intermediary. Reaction mixtures were sampled periodically and chromatographed directly by HPLC on a silica gel column, by using isocratic elution with mixtures of hexane-ethanol-acetic acid in several different proportions. The degree of reaction completion was determined by comparison of the peak area of the initial reactant to that present at sampling time. MPA oxime production was found to be complete after 15 min; 97.0% of the oxime was converted to succinimide ester in 24 h; 99.0% of the available ester reacted within 2.5 h to form the final labelled product. Zearalanone oxime production was found to be complete after 2 h; 93.3% of the oxime was converted to the activated ester within 24 h; 89.6% of available ester had reacted in 30 min to form the final labelled product. The chromatography can be performed in real time, permitting modification in the conditions of the reaction while in progress.

Chemical Phenomena

Systemic absorption of metronidazole by the vaginal route.

A study was designed to compare the systemic absorption of metronidazole by the oral and vaginal routes. Nine subjects received single 500-mg doses of the oral, vaginal insert, and vaginal cream preparations on three occasions. Approximately 20% bioavailability was demonstrated from both vaginal forms. Mean peak plasma concentrations were 15.56 micrograms/mL for the oral form, 1.86 micrograms/mL for the cream, and 1.89 micrograms/mL for the insert. The mean times to peak concentration were 1.23 hours for the oral dose and 11.11 hours and 20.11 hours for the cream and insert, respectively. The data demonstrate that some vaginal absorption occurs from both the cream and insert preparations of metronidazole.

Absorption

The estimation of quinidine in human plasma by ion pair extraction and high-performance liquid chromatography.

A rapid, sensitive, accurate method for determination of quinidine in plasma has been developed using ion-pair extraction and high-performance liquid chromatography. The method, which is capable of distinguishing between quinidine and dihydroquinidine, involves acidification of plasma with perchloric acid, extraction with methyl isobutyl ketone and chromatography of the carbonate-washed extract on a silica gel column with a mobile phase of methylene chloride-hexane-methanol--perchloric acid (60:35:5.5:0.1) followed by fluorometric detection. The procedure is sensitive to below 50 ng/ml (coefficient of variation 6.6%) and compares favourably with a standard spectrofluorometric method when tested with plasma from volunteer subjects.

Chromatography, High Pressure Liquid

High performance liquid chromatographic and mass spectrometric identification of dimethylxanthine metabolites of caffeine in human plasma.

High performance liquid chromatography and mass spectrometry were used to isolate and identify theophylline, theobromine and 1,7-dimethylxanthine (paraxanthine) in plasma of human volunteers following administration of 300 mg caffeine to methylxanthine-free volunteers. Plasma from these subjects was extracted and the dimethylxanthines were separated from each other and caffeine by high performance liquid chromatography. The effluents at the chromatographic peaks corresponding to the dimethylxanthine metabolites were collected, rechromatographed in a second system and the dried residues were subjected to mass spectrometry. By comparison of their retention times and mass spectra with those of authentic compounds, theophylline, theobromine and paraxanthine were positively identified as metabolic products of caffeine.

Caffeine

Bioavailability of three isoniazid formulations.

The bioavailability of three isoniazid formulations was assessed using a procedure specific for the free drug. Nine human volunteers, all slow acetylators, were each given 4 X 100 mg of isoniazid of three different tablet formulations at weekly intervals; the plasma drug levels were measured at different times during the first 24 hr. No significant differences (p greater than 0.05) were detected among the three products as to relative bioavailability, peak plasma concentrations, Cmax, and the time of Cmax, tmax. Analysis of variance of the pharmacokinetic parameters obtained according to a one-compartment open model did not demonstrate any significant formulation or time effect but revealed a significant intersubject variation in all parameters involved.

Adult

Simultaneous assay of the methylxanthine metabolites of caffeine in plasma by high performance liquid chromatography.

A fast and sensitive method by high performance liquid chromatography for the quantification of the methylxanthine metabolites of caffeine in human plasma is described. Plasma is extracted with 20% isopropanol in chloroform and the evaporated residue is redissolved and chromatographed on silica gel using dichloromethane containing 2.2% of a solution of methanol-ammonium formateformic acid (100:0.02:0.017). The method is suitable for metabolic and pharmacokinetic studies of all mono- and dimethylxanthines in plasma. The limits of quantification, with C.V. of 10% or less are 40 ng/ml for the dimethylxanthines, 100 ng/ml for 3- and 7-methylxanthine and 500 ng/ml for 1-methylxanthine.

Caffeine

Assay of sulfonylureas in human plasma by high-performance liquid chromatography.

A sensitive and specific high-performance liquid chromatographic procedure for the determination of chlorpropamide or tolbutamide in plasma in the presence of their metabolites is described. The ether extract of acidified plasma is redissolved in the mobile phase, 17% acetonitrile in 0.05 M aqueous ammonium formate, and chromatographed on a reverse-phase column on a high-performance liquid chromatograph fitted with a UV absorbance detector. Quantitation of plasma samples containing less than 0.5 mug/ml of chlorpropamide and 5 mug/ml of tolbutamide is reported, using these drugs as mutual internal standards. The retention times of the metabolites are such that they do not interfere in the procedure. The assay method was tested in a human volunteer with both drugs and found suitable for single-dose pharmacokinetic studies.

Chlorpropamide

The human metabolism of caffeine to theophylline.

Theophylline peak plasma concentration of over 170 ng/ml average was observed when 300 mg of caffeine, equivalent to 2-3 cups of coffee, was administered to humans. This peak level was not observed until at least 7 hr post administration. Accumulation of caffeine, with its subsequent metabolism to theophylline, in patients, who consume average quantities of caffeine-containing beverages relative to those patients who avoid such drinks could interfere with bioavailability studies in normal volunteers. However, it may account for only a small portion of the variable clinical effects associated with aminophylline administration.

Allopurinol

The identification and assay of 2-methyl-5-nitroimidazole in pigs treated with dimetridazole.

An unidentified metabolite of dimetridazole (DMZ), found in pig plasma, muscle and kidney, was shown by chromatography and spectroscopy to be 2-methyl-5-nitroimidazole (2-MNI), resulting from N-demethylation of DMZ. This route of degradation competes with the oxidation pathway previously described. The concentration of 2-MNI in the plasma of pig fed medicated diet (DMZ 0.0125%) ranged from 29 to 83 ppb, 2 hours after the morning meal, similar to DMZ, but lower than that of the major metabolite, 2-hydroxymethyl-1-methyl-5-nitroimidazole (HMMNI). Its elimination profile in plasma was biphasic, similar to those of HMMNI and DMZ. Early and terminal half lives were 2.6 and 9.1 h respectively. None of the metabolites could be detected in any of the tissues studied 49 hours after withdrawal.

Animals

Separation, identification and determination of lumichrome in swine feed and kidney.

During surveillance of hog carcasses from Manitoba for antibiotic residues by the Health of Animals Laboratory, Agriculture Canada, Saskatoon, an unknown substance was found which produced tetracycline-like results with the methods used. This same substance was found in an implicated swine feed premix. Using various HPLC systems and columns, UV spectroscopy, reverse-phase TLC, and mass spectrometry, the substance was isolated from the feed premix, and identified as lumichrome, a photodegradation product of riboflavin. Traces of the same substance were found in riboflavin standard. Analysis of swine kidney, previously found to contain the unknown, showed the same substance was present at a level of about 1 ppm.

Animal Feed

Assay of oxolinic acid residues in salmon muscle by liquid chromatography with fluorescence detection: interlaboratory study.

A previously developed method that uses a simplified sample preparation and fluorometric detection of liquid chromatographic eluates for the determination of oxolinic acid in salmon muscle has been collaboratively studied. Five laboratories participated in the study to analyze, in quintuplicate, blank salmon muscle fortified at 10, 20, 50, and 100 micrograms/kg (ppb), and 2 incurred samples from salmon given feed with medicated oxolinic acid. The tissue, 2 g mixed with 2 g Na2SO4, is extracted with ethyl acetate and centrifuged, and the solvent is evaporated. The residue is partitioned in a mixture of hexane and 0.01 M oxalic acid, and the aqueous phase is chromatographed using fluorescence detection at 327 nm excitation and 369 nm emission. Mean recoveries ranged from 77.2 to 84.5% in spiked samples with reproducibility relative standard deviation (RSDR) ranging from 11.5 to 18.3%. Treated salmon were found to contain 8.71 and 53.8 micrograms/kg with RSDR of 18.6 and 16.7%, respectively. The corresponding repeatability relative standard deviations (RSDR) were 5.8-12.2%, and 7.7 and 6.2%. The method is recommended for regulatory purposes in Canada.

Animals

Determination of oxolinic acid residues in salmon muscle tissue by liquid chromatography with fluorescence detection.

The present paper describes a method for determination of oxolinic acid in salmon muscle tissue. Tissue (0.5-2 g) mixed with 2 g anhydrous sodium sulfate is extracted twice with ethyl acetate, centrifuged, and the extract evaporated. The residue is partitioned in a mixture of hexane and 0.01M oxalic acid and the aqueous phase chromatographed using fluorescence detection at 327 nm excitation and 369 nm emission. Calibration and standard curves are linear from 10-200 ppb and 100-2000 ppb at different sensitivity settings. Recoveries ranged from 71-83% in spiked blanks, with a CV of 4-10.3% over a 2-week period. Preliminary results in treated salmon were variable, possibly because some fish refused to eat medicated feed.

Animals